Alcohol is mentioned frequently in the novel, sometimes generally and sometimes in direct reference to the various characters. Gatsby, we learn, did not drink; as a young man sailing with Dan Cody, he had observed the detrimental effects of alcohol and had chosen to avoid them. In another way, however, Gatsby was influenced by alcohol. As a bootlegger during Prohibition during the 1920s, much of Gatsby's fortune came from its illegal sale.

At one significent time in Daisy's life, she became very drunk. The evening before her wedding to Tom Buchanan, Daisy was overcome with despair, still in love with her lieutenant, Jay Gatsby. Jordan Baker found her with "a bottle of sauterne in one hand" and a letter from Gatsby in another. This was, in fact, the first time Daisy had ever tasted alcohol, and she had become "as drunk as a monkey." Under the influence of alcohol, her true feelings poured out; she wanted to cancel her wedding, and she "cried and cried" for Gatsby. When she sobered up, Daisy attended that evening's bridal party and married Tom the following day.

Nick becomes drunk for the second time in his life when he attends the party at Tom and Myrtle's apartment in New York, the day of his thirtieth birthday. Usually a very responsible, conservative young man, Nick wakes up in Pennsylvania Station waiting for the train at 4:00 am, with some of the previous evening a blur in his memory. Recalling the events of the party, Nick comments that "everything that happened has a dim hazy cast over it."

Finally, the negative aspects of Tom Buchanan's personality are accentuated when he is drinking. At the party Nick attended, Tom has been drinking all afternoon and into the evening. He becomes aggressive and belligerent with Myrtle, ultimately breaking her nose during a violent quarrel. Also, Tom has been drinking when he confronts Gatsby in the hotel room in New York; his arrogance, contempt, and hatred for Gatsby are released in a torrent of insults and accusations. He would have attacked him physically had others not intervened.